Motor cortex metabolite alterations in amyotrophic lateral sclerosis assessed in vivo using edited and non-edited magnetic resonance spectroscopy.

Previous MRI and proton spectroscopy (1H-MRS) studies have revealed impaired neuronal integrity and altered neurometabolite concentrations in the motor cortex of patients with amyotrophic lateral sclerosis (ALS). Here, we aim to use MRI with conventional and novel MRS sequences to further investigate neurometabolic changes in the motor cortex of ALS patients and their relation to clinical parameters. We utilized the novel HERMES (Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy) MRS sequence to simultaneously quantify the inhibitory neurotransmitter GABA and antioxidant glutathione in ALS patients (n = 7) and healthy controls (n = 7). In addition, we have also quantified other MRS observable neurometabolites using a conventional point-resolved MR spectroscopy (PRESS) sequence in ALS patients (n = 20) and healthy controls (n = 20). We observed a trend towards decreasing glutathione concentrations in the motor cortex of ALS patients (p = 0.0842). In addition, we detected a 11% decrease in N-acetylaspartate (NAA) (p = 0.025), a 15% increase in glutamate + glutamine (Glx) (p = 0.0084) and a 21% increase in myo-inositol (mIns) (p = 0.0051) concentrations for ALS patients compared to healthy controls. Furthermore, significant positive correlations were found between GABA-NAA (p = 0.0480; Rρ = 0.7875) and NAA-mIns (p = 0.0448; Rρ = -0.4651) levels among the patients. NAA levels in the bulbar-onset patient group were found to be significantly (p = 0.0097) lower compared to the limb-onset group. A strong correlation (p < 0.0001; Rρ = -0,8801) for mIns and a weak correlation (p = 0.0066; Rρ = -0,6673) for Glx was found for the disease progression, measured by declining of the ALS Functional Rating Scale-Revised criteria (ALSFRS-R). Concentrations of mIns and Glx also correlated with disease severity measured by forced vital capacity (FVC). Results suggest that mean neurometabolite concentrations detected in the motor cortex may indicate clinical and pathological changes in ALS.

Thyrotoxic periodic paralysis: an unusual presentation of hyperthyroidism.

Thyrotoxic periodic paralysis (TPP) is a complication of hyperthyroidism among Asians, characterised by sudden onset of hypokalaemia and muscle paralysis. Several factors may contribute to a delay in diagnosis, including the subtlety of hyperthyroidism, the transient nature of the events and the rarity of this disease in the West. As life-threatening arrhythmias may occur during an attack, awareness among physicians is necessary for early recognition and treatment. Advances have been made in understanding the pathophysiological mechanism leading to hypokalaemia, which include recently identified mutations of the inwardly rectifying potassium channel Kir2.6. Treatment includes the supplementation of potassium, a nonselective beta-blocker, and ultimately treatment of the underlying hyperthyroidism. Here we report three cases of TPP in the Netherlands, and review the literature on clinical features, pathophysiological hypothesis and treatment.

Intermediate and long-term adverse effects of radioiodine therapy for differentiated thyroid carcinoma--a systematic review.

BACKGROUND: Treatment of differentiated thyroid carcinoma (DTC) often involves administration of radioactive iodine (I-131) for remnant ablation or adjuvant therapy. As DTC has favorable outcome and the incidence is increasing, concerns have been raised about the possible adverse effects of I-131 therapy. We systematically reviewed the literature to examine the risk of intermediate and long-term adverse effects of I-131 therapy in DTC patients. METHODS: Multiple electronic databases were searched up to November 2014 for English-language, controlled studies that reported on the risk of salivary gland dysfunction, lacrimal gland dysfunction, gonadal dysfunction, female reproductive outcomes or second primary malignancies (SPM) after I-131 exposure. The certainty of the evidence found was assessed using GRADE. RESULTS: In total, 37 articles met all inclusion criteria, no studies reporting on adverse effects after I-131 treatment focused solely on children. After exposure to I-131 for DTC, patients experienced significantly more frequently salivary gland dysfunction (prevalence range: 16-54%, moderate-level evidence), lacrimal gland dysfunction (prevalence: 11%, low-level evidence), transient male gonadal dysfunction (prevalence: 35-100%, high-level evidence), transient female gonadal dysfunction (prevalence: 28%, low-level evidence) and SPM (prevalence: 2.7-8.7%, moderate-level evidence) compared to unexposed patients. I-131 therapy seems to have no deleterious effects on female reproductive outcomes (very-low level evidence). The prevalence and severity of adverse effects were correlated to increasing cumulative I-131 activity. CONCLUSION: Treatment with I-131 for DTC may have significant adverse effects, which seem to be dose dependent. These adverse effects of treatment must be balanced when choosing for I-131 therapy in patients with DTC.

Spinal cord stimulation modulates cerebral function: an fMRI study.

INTRODUCTION: Although spinal cord stimulation (SCS) is widely used for chronic neuropathic pain after failed spinal surgery, little is known about the underlying physiological mechanisms. This study aims to investigate the neural substrate underlying short-term (30 s) SCS by means of functional magnetic resonance imaging in 20 patients with failed back surgery syndrome (FBSS). METHODS: Twenty patients with FBSS, treated with externalized SCS, participated in a blocked functional magnetic resonance imaging design with stimulation and rest phases of 30 s each, repeated eight times in a row. During scanning, patients rated pain intensity over time using an 11-point numerical rating scale with verbal anchors (0 = no pain at all to 10 = worst pain imaginable) by pushing buttons (left hand, lesser pain; right hand, more pain). This scale was back projected to the patients on a flat screen allowing them to manually direct the pain indicator. To increase the signal-to-noise ratio, the 8-min block measurements were repeated three times. RESULTS: Marked deactivation of the bilateral medial thalamus and its connections to the rostral and caudal cingulate cortex and the insula was found; the study also showed immediate pain relief obtained by short-term SCS correlated negatively with activity in the inferior olivary nucleus, the cerebellum, and the rostral anterior cingulate cortex. CONCLUSIONS: Results indicate the key role of the medial thalamus as a mediator and the involvement of a corticocerebellar network implicating the modulation and regulation of averse and negative affect related to pain. The observation of a deactivation of the ipsilateral antero-medial thalamus might be used as a region of interest for further response SCS studies.

Non invasive in vivo anatomical studies of the oscine brain by high resolution MRI microscopy.

We describe in this paper an in vivo Magnetic Resonance Imaging (MRI) procedure that allows one to obtain three-dimensional high quality images of the entire brain of small passerine birds such as the canary with a slice thickness of 58 micron and an image resolution of 78 microns. This imaging procedure was completed in 70 min on anaesthetised birds that later recovered uneventfully and could be reused for subsequent additional imaging. To illustrate the high resolution and anatomical detail that can be achieved, examples of coronal images through the entire hypothalamus are provided in the same sectioning plane as the previously published canary brain atlas. The data set can be used to create sections in any desired plane and the entire data set can be viewed from any point of view in a volume rendered image. This provides a useful tool in understanding the three-dimensional organisation of the brain. Similar procedures can also be applied on fixed brains and might allow an even better anatomical resolution of images because time constrains no longer limit the duration of image acquisition. The non-invasive MRI technique enables to study neuroanatomical features with a high resolution and without killing the animal subjects so that measures can be obtained in a same individual both before and after an experimental treatment.

[No difference in effectiveness measured between treatment in a thermal bath and in an exercise bath in patients with rheumatoid arthritis]. / Geen verschil in effectiviteit gemeten tussen behandeling in een thermaalbad en in een oefenbad bij patiënten met reumatoïde artritis.

OBJECTIVE: To determine whether hydrotherapy in a thermomineral institution is superior to the same hydrotherapy in an ordinary hospital exercise-bath. DESIGN: Controlled therapeutic trial. SETTING: The thermomineral institution at Arcen and the exercise bath at the Maasland Hospital in Sittard, the Netherlands. PATIENTS AND METHODS: 46 patients with rheumatoid arthritis were treated in a by a skilled physiotherapist, according to a standardized exercise-scheme: 27 were treated in the thermomineral institution and 19 (control-group) in the hospital exercise-bath. Each patient received 12 treatments in 12 weeks. ENDPOINTS PARAMETERS: Morning stiffness, erythrocyte sedimentation rate, Ritchie index, amount of pain, answers to 11 questions concerning the activities of daily life, and psychosocial aspects of the disease. The various subjective and objective parameters were scored by the same physician. RESULTS: Statistically significant improvement was observed in both groups concerning morning stiffness. Other subjective parameters improved, but did not reach significance. Objective parameters did not change significantly. Between-group differences were not found. CONCLUSION: Hydrotherapy has a positive effect on some subjective but not on objective parameters in patients with rheumatoid arthritis, whether it is applied in a thermomineral institution or an ordinary hospital exercise bath.

Perinatal mortality and morbidity in rural West-Java, Indonesia. Part II: The results of a longitudinal survey on pregnant women.

The main objective of this prospective survey is to obtain more information on the natural history of pregnancy and its outcome, including low birth weights, and of the factors closely associated with it. During the survey period the birth rate was 40 per thousand and the perinatal death rate 48 per thousand. The main causes of neonatal deaths are infections (predominantly tetanus) and hypoxia/birth asphyxia. Perinatal mortality is significantly associated with the following risk factors: age of mother less than 20 years; birth interval shorter than 18 months, twins, and breech presentation. The incidence of low birth weight is 14.7%. Statistically significant associations have been found between low birth weight and several risk factors.

PIP: Traditional birth attendants made 5 home visits to each pregnant woman in Ujung-Berung area of rural West Java in Indonesia between September 1978-February 1980 to determine the natural history of pregnancy and its outcome and the factors associated with the different outcomes. They performed 87% of the deliveries. 4 mothers died (1.7% of all live births). The birth rate was 40% and 2335 infants were born. The perinatal mortality rate stood at 44.5. The percentage of fetal deaths was 13.7% (32) and of early neonatal deaths was 31.2% (72). The leading cause of early neonatal death was infection (50.2%) and tetanus neonatorum contributed to mortality in 79% of these cases (case fatality rate 100%). In the early neonatal period, the tetanus specific perinatal mortality was 17%. Further it stood at a high of 9.5/1000 live births due to low tetanus immunization coverage. Intrauterine hypoxia and birth asphyxia contributed the most to perinatal deaths (57.8%) followed by infections (23.6%). Twin births posed 4.14 times the risk of perinatal mortality than did singleton births (p.05). The single most significant risk factor for perinatal mortality, however, was breech delivery (relative risk [RR] 5.7; p.05). Mother's age 20 years (RR 1.28) and birth interval between 6-17 months (2.76) comprised the only other 2 significant risk factors (p.05). 14.7% of the infants weighed 2500 g. For low birth weight (LBW) infants, twin births posed the greatest risk to mortality (RR 5.65) followed by complications before delivery (RR 3.7), breech birth (RR 2.3), and 1st birth (RR 2.06) [all significant at p.05]. LBW infants had a high percentage of illnesses during the neonatal period (30.2%). Overall morbidity during this time stood at 16.9%.